BACKGROUND: Multiple epidemiological studies have observed the connection between aging and brain volumes. The concept of accelerated biological aging (BA) is more powerful for observing the degree of aging of an individual than chronologic age (CA). The objective of this study is to explore the relationship between BA and brain volumes.
METHODS: BA was measured from clinical traits using two blood-chemistry algorithms, the Klemera-Doubal method (KDM) and the PhenoAge. The two age acceleration biomarkers were calculated by the residuals from regressing CA, termed \"KDM-acceleration\" and \"PhenoAge-acceleration\". Brain volumes were from brain magnetic resonance imaging (MRI) data. After adjustment for confounding factors, general linear regression models were used to examine associations between KDM-acceleration and PhenoAge-acceleration and brain volumes, respectively. Additionally, we stratified participants by sex, age, and the four quartiles of the Townsend Deprivation Index (TDI) for extra subgroup analysis.
RESULTS: 14,725 participants with available information were enrolled. After full adjustment, we observed negative associations between KDM-acceleration and brain volumes, such as gray matter (β = -0.029), white matter (β = -0.021), gray and white matter (β = -0.026), and hippocampus (β = -0.011 for left and β = -0.014 for right). There were also negative associations between PhenoAge-acceleration and brain volumes, such as white matter (β = -0.008), gray and white matter (β = -0.010), thalamus (β = -0.012 for left and β = -0.012 for right). In the subgroup analysis stratified by sex, age, and the four quartiles of TDI, the association between KDM-acceleration and PhenoAge-acceleration and brain volumes still existed. In subgroup analyses, the variation in associations suggests that socioeconomic and biological factors may differentially influence brain aging.
CONCLUSIONS: Our research indicated that more advanced BA was associated with less brain tissue.

BACKGROUND: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy.
METHODS: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method.
RESULTS: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen\'s d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen\'s d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen\'s d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS.
CONCLUSIONS: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults.

UNASSIGNED: Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife.
UNASSIGNED: Baseline (n = 612) and five-year follow-up (n = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors.
UNASSIGNED: Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes.
UNASSIGNED: Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.

UNASSIGNED: The relative importance of different components of cognitive reserve (CR), as well as their differences by gender, are poorly established.
UNASSIGNED: To explore several dimensions of CR, their differences by gender, and their effects on cognitive performance and trajectory in a cohort of older people without relevant psychiatric, neurologic, or systemic conditions.
UNASSIGNED: Twenty-one variables related to the education, occupation, social activities, and life habits of 1,093 home-dwelling and cognitively healthy individuals, between 68 and 86 years old, were explored using factorial analyses to delineate several dimensions of CR. These dimensions were contrasted with baseline cognitive performance, follow-up over 5 years of participants\' cognitive trajectory, conversion to mild cognitive impairment (MCI), and brain volumes using regression and growth curve models, controlling for gender, age, marital status, number of medications, trait anxiety, depression, and ApoE genotype.
UNASSIGNED: Five highly intercorrelated dimensions of CR were identified, with some differences in their structure and effects based on gender. Three of them, education/occupation, midlife cognitive activities, and leisure activities, were significantly associated with late-life cognitive performance, accounting for more than 20% of its variance. The education/occupation had positive effect on the rate of cognitive decline during the 5-year follow up in individuals with final diagnosis of MCI but showed a reduced risk for MCI in men. None of these dimensions showed significant relationships with gray or white matter volumes.
UNASSIGNED: Proxy markers of CR can be represented by five interrelated dimensions. Education/occupation, midlife cognitive activities, and leisure activities are associated with better cognitive performance in old age and provide a buffer against cognitive impairment. Education/occupation may delay the clinical onset of MCI and is also associated with the rate of change in cognitive performance.

UNASSIGNED: Women carrying the APOE4 allele are at greater risk of developing Alzheimer\'s disease (AD) from ages 65-75 years compared to men. To better understand the elevated risk conferred by APOE4 carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and APOE4 carrier status on regional brain volumes in a sample of late midlife postmenopausal women.
UNASSIGNED: Participants were enrolled in MsBrain, a cohort study of postmenopausal women (n = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, APOE4 carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography-tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aβ42/Aβ40, Aβ42/p-tau181), and APOE4 carrier status predict regional brain volume (21 regions per hemisphere, selected a priori); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by APOE4 carrier status.
UNASSIGNED: There was no main effect of APOE4 carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and APOE4 carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aβ42/40, lower Aβ42/p-tau181 ratios). In APOE4-stratified analyses, these interactions were driven by non-APOE4 carriers.
UNASSIGNED: We demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-APOE4 carriers, suggesting that APOE4 carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

UNASSIGNED: Language disturbances are a core feature of schizophrenia, often studied as a formal thought disorder. The neurobiology of language in schizophrenia has been addressed within the same framework, that language and thought are equivalents considering symptoms and not signs. This review aims to systematically examine published peer-reviewed studies that employed neuroimaging techniques to investigate aberrant brain-language networks in individuals with schizophrenia in relation to linguistic signs.
UNASSIGNED: We employed a language model for automatic data extraction. We selected our studies according to the PRISMA recommendations, and we conducted the quality assessment of the selected studies according to the STROBE guidance.
UNASSIGNED: We analyzed the findings from 37 studies, categorizing them based on patient characteristics, brain measures, and language task types. The inferior frontal gyrus (IFG) and superior temporal gyrus (STG) exhibited the most significant differences among these studies and paradigms.
UNASSIGNED: We propose guidelines for future research in this field based on our analysis. It is crucial to investigate larger networks involved in language processing, and language models with brain metrics must be integrated to enhance our understanding of the relationship between language and brain abnormalities in schizophrenia.

Gestational exposure to valproic acid (VPA) is a risk factor for autism spectrum disorder (ASD). Rodents exposed to VPA in utero display common features of ASD, including volumetric dysregulation in higher-order cognitive regions like the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus. Exercise has been shown in elderly populations to boost cognition and to buffer against brain volume losses with age. This study employed an adolescent treadmill exercise intervention to facilitate cognitive flexibility and regional brain volume regulation in rats exposed to VPA during gestation. It was found that exercise improved performance on extra-dimensional shifts of attention on a set-shifting task, which is indicative of improved cognitive flexibility. Exercise decreased frontal cortex volume in females, whereas in males exercise increased the ventral hippocampus. These findings suggest that aerobic exercise may be an effective intervention to counteract the altered development of prefrontal and hippocampal regions often observed in ASD.

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults.
METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil.
RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison.
CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.

OBJECTIVE: To examine the associaiton between environmental measures and brain volumes and its potential mediators.
METHODS: This was a prospective study.
METHODS: Our analysis included 34,454 participants (53.4% females) aged 40-73 years at baseline (between 2006 and 2010) from the UK Biobank. Brain volumes were measured using magnetic resonance imaging between 2014 and 2019.
RESULTS: Greater proximity to greenspace buffered at 1000 m at baseline was associated with larger volumes of total brain measured 8.8 years after baseline assessment (standardized β (95% CI) for each 10% increment in coverage: 0.013(0.005,0.020)), grey matter (0.013(0.006,0.020)), and white matter (0.011(0.004,0.017)) after adjustment for covariates and air pollution. The corresponding numbers for natural environment buffered at 1000 m were 0.010 (0.004,0.017), 0.009 (0.004,0.015), and 0.010 (0.004,0.016), respectively. Similar results were observed for greenspace and natural environment buffered at 300 m. The strongest mediator for the association between greenspace buffered at 1000 m and total brain volume was smoking (percentage (95% CI) of total variance explained: 7.9% (5.5-11.4%)) followed by mean sphered cell volume (3.3% (1.8-5.8%)), vitamin D (2.9% (1.6-5.1%)), and creatinine in blood (2.7% (1.6-4.7%)). Significant mediators combined explained 18.5% (13.2-25.3%) of the association with total brain volume and 32.9% (95% CI: 22.3-45.7%) of the association with grey matter volume. The percentage (95% CI) of the association between natural environment and total brain volume explained by significant mediators combined was 20.6% (14.7-28.1%)).
CONCLUSIONS: Higher coverage percentage of greenspace and environment may benefit brain health by promoting healthy lifestyle and improving biomarkers including vitamin D and red blood cell indices.